Interleukin-1alpha secreted by pancreatic cancer cells promotes angiogenesis and its therapeutic implications.
BACKGROUND
Previously we reported the critical role of interleukin (IL)-1alpha in liver metastasis from pancreatic cancer (PaCa). However, its role in angiogenesis and metastasis, particularly as it relates to the interaction between tumor and stromal cells, was not clearly elucidated. To further investigate, we initially compared vascular endothelial cell migration and tube formation in human PaCa cell lines that differed in metastatic potential. We then compared the effects of IL-1alpha derived from PaCa cells on the same processes.


METHODS
Expression of IL-1alpha mRNA and protein in PaCa cells was measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. IL-1alpha mRNA and protein were detected only in predominantly liver-metastatic PaCa cells. Next, we examined differences in migration and tube formation by human umbilical vein endothelial cells (HUVECs) in the various PaCa cells using invasion and angiogenesis assays, respectively. Furthermore, we determined the effects of IL-1alpha secreted by PaCa cells on migration and tube formation by HUVECs using coculture experiments.


RESULTS
Expression of IL-1alpha mRNA and protein was observed only by the highly liver-metastatic PaCa cell lines BxPC-3 and SW 1990. Both HUVEC migration and tube formation were significantly enhanced by coculture with metastatic PaCa cells and IL-1alpha (P < 0.01). Similarly, blockade of IL-1alpha by its antagonist inhibited HUVEC migration and tube formation (P < 0.01).


CONCLUSIONS
Our results indicate that IL-1alpha secreted by PaCa cells plays an important role in metastasis through vascular endothelial cell invasion and angiogenesis. Thus, blocking IL-1alpha is a potential novel therapeutic strategy in PaCa.
Matsuo
Yoichi
Y
Department of Gastroenterology, Hepatology, and Nutrition, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Sawai
Hirozumi
H
Ochi
Nobuo
N
Yasuda
Akira
A
Takahashi
Hiroki
H
Funahashi
Hitoshi
H
Takeyama
Hiromitsu
H
Guha
Sushovan
S
D045744:Cell Line, Tumor; D054443:Cell Migration Assays; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006801:Humans; D053582:Interleukin-1alpha / Q000502:physiology*; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism
D053582:Interleukin-1alpha; D012333:RNA, Messenger